Stress as necessary component of realistic recovery in animal models of experimental stroke

Over the last decade there has been a considerable effort directed toward reformulating the standard approach taken to preclinically model stroke and stroke recovery. The principal objective of this undertaking has been to improve the success with which preclinical findings can be translated. Although several advancements have already been introduced, one potentially critical feature that appears to have been overlooked is psychological stress. Stroke is well recognized to produce high levels of stress in patients, and ongoing exposure to stress is recognized to deleteriously interfere with recovery. The presence of high levels of stress (distress) in stroke patients is also relevant because nearly all clinically deployed neurorestorative interventions occur against this background. Somewhat perplexingly, however, we could find no preclinical stroke studies concerned with investigating the efficacy of putative neurorestorative compounds that did so in the presence of stress. The following article will make the case that failure to recognize or compensate for the effects of ongoing stress in standard preclinical experimental models of recovery is likely to result in overestimation of the effectiveness of pharmacological or behavioral neurorestorative interventions.